Goossens A, Dever T E, Pascual-Ahuir A, Serrano R
Instituto de Biologia Molecular y Celular de Plantas, Universidad Politécnica de Valencia-C.S.I.C., Camino de Vera s/n, 46022 Valencia, Spain.
J Biol Chem. 2001 Aug 17;276(33):30753-60. doi: 10.1074/jbc.M102960200. Epub 2001 Jun 14.
Phosphorylation of the alpha-subunit of eukaryotic initiation factor 2 (eIF2alpha) is a conserved mechanism regulating protein synthesis in response to various stresses. A screening for negative factors in yeast salt stress tolerance has led to the identification of Gcn2p, the single yeast eIF2alpha kinase that is activated by amino acid starvation in the general amino acid control response. Mutation of other components of this regulatory circuit such as GCN1 and GCN3 also resulted in improved NaCl tolerance. The gcn2 phenotype was not accompanied by changes in sodium or potassium homeostasis. NaCl induced a Gcn2p-dependent phosphorylation of eIF2alpha and translational activation of Gcn4p, the transcription factor that mediates the general amino acid control response. Mutations that activate Gcn4p function, such as gcd7-201, cpc2, and deletion of the translational regulatory region of the GCN4 gene, also cause salt sensitivity. It can be postulated that sodium activation of the Gcn2p pathway has toxic effects on growth under NaCl stress and that this novel mechanism of sodium toxicity may be of general significance in eukaryotes.
真核生物起始因子2（eIF2α）的α亚基磷酸化是一种保守机制，可响应各种应激调节蛋白质合成。对酵母耐盐胁迫负调控因子的筛选，鉴定出了Gcn2p，它是酵母中唯一的eIF2α激酶，在一般氨基酸控制反应中被氨基酸饥饿激活。该调节回路其他组分（如GCN1和GCN3）的突变也导致对NaCl耐受性提高。gcn2表型并未伴随钠或钾稳态的变化。NaCl诱导Gcn2p依赖的eIF2α磷酸化以及Gcn4p的翻译激活，Gcn4p是介导一般氨基酸控制反应的转录因子。激活Gcn4p功能的突变，如gcd7 - 201、cpc2以及GCN4基因翻译调控区的缺失，也会导致盐敏感性。可以推测，Gcn2p途径的钠激活在NaCl胁迫下对生长具有毒性作用，并且这种新的钠毒性机制可能在真核生物中具有普遍意义。
